Search

It has long been hypothesized that abnormalities in lipid biology contribute to degenerative brain diseases. Consistent with this, emerging epidemiologic evidence links lipid alterations with Parkinson disease (PD), and disruption of lipid metabolism has been found to predispose to α -synuclein toxicity. We therefore investigated whether Parkin, an E3 ubiquitin ligase found to be defective in patients with early onset PD, regulates systemic lipid metabolism. We perturbed lipid levels by exposing (Parkin.sup.+/+) and [Parkin.sup.-/-] mice to a high-fat and -cholesterol diet (HFD). Parkin.sup.-/-) mice resisted weight gain, steatohepatitis, and insulin resistance. In wild-type mice, the HFD markedly increased hepatic Parkin levels in parallel with lipid transport proteins, including CD36, Sr-B1, and FABP. These lipid transport proteins were not induced in [Parkin.sup.-/-] mice. The role of Parkin in fat uptake was confirmed by increased oleate accumulation in hepatocytes overexpressing Parkin and decreased uptake in [Parkin.sup.-/-] mouse embryonic fibroblasts and patient cells harboring complex heterozygous mutations in the Parkin-encoding gene PARK2. Parkin conferred this effect, in part, via ubiquitin-mediated stabilization of the lipid transporter CD36. Reconstitution of Parkin restored hepatic fat uptake and CD36 levels in [Parkin.sup.-/-] mice, and Parkin augmented fat accumulation during adipocyte differentiation. These results demonstrate that Parkin is regulated in a lipid-dependent manner and modulates systemic fat uptake via ubiquitin ligase-dependent effects. Whether this metabolic regulation contributes to premature Parkinsonism warrants investigation., Introduction PARK2 mutations associate with an autosomal recessive juvenile form of Parkinson disease (PD) (1). However, the role of Parkin in the development of PD in mice is surprisingly modest, [...]

Tat activating regulatory DNA-binding protein (Tardbp or TDP-43), a highly conserved metazoan DNA/RNA binding protein thought to be involved in RNA transcription and splicing, has been linked to the pathophysiology of amyotrophic lateral sclerosis and fronto-temporal lobar degeneration and is essential for early embryonic development. However, neither the physiological role of TDP-43 in the adult nor its downstream targets are well defined. To address these questions, we developed conditional Tardbp-KO mice and embryonic stem (ES) cell models. Here, we show that postnatal deletion of Tardbp in mice caused dramatic loss of body fat followed by rapid death. Moreover, conditional Tardbp-KO ES cells failed to proliferate. Importantly, high-throughput DNA sequencing analysis on the transcriptome of ES cells lacking Tardbp revealed a set of downstream targets of TDP-43. We show that Tbc1d1, a gene known to mediate leanness and linked to obesity, is down-regulated in the absence of TDP-43. Collectively, our results establish that TDP-43 is critical for fat metabolism and ES cell survival. conditional knockout mice | amyotrophic lateral sclerosis | frontotemporal dementia | energy metabolism | RNA-sequencing www.pnas.org/cgi/doi/ 10.1073/pnas.1002176107

Expression of the GH receptor (GHR) gene and its binding with GH is essential for growth and fat metabolism. A GT microsatellite exists in the promoter of bovine GHR segregating short (11 bp) and long (16 to 20 bp) allele sequences. To detect SNP and complete an association study of genotype to phenotype, we resequenced a 1,195-bp fragment of DNA including the GT microsatellite and exon 1A. Resequencing was completed in 48 familialy unrelated Holstein, Jersey, Brown Swiss, Simmental, Angus, Brahman, and Brangus cattle. Nine SNP were identified. Phylogeny analyses revealed minor distance (i.e., Key words: bovine, Brangus, deoxyribonucleic acid, growth hormone receptor, single nucleotide polymorphism

Dietary fibers may modulate insulin resistance and glucose homeostasis in dogs. Their efficacy is, however, dependent on their origin, physical properties, and fermentability in the large bowel. Eight healthy Beagle dogs were fed a commercial diet at twice their maintenance requirements until they became obese. They were then maintained in the obese state and used in a cross-over design study to evaluate the effects of short-chain fructooligosaccharide (scFOS) supplementation (1% wt:wt dry matter in the diet). The euglycemic hyperinsulinemic clamp technique was performed before and after fattening and at the end of each 6-wk cross-over period. Fat tissue biopsies were taken in food-deprived and postprandial phases to measure mRNA abundance of genes involved with fatty acid, glucose metabolism, or inflammation. Insulin resistance appeared progressively with fattening and the rate of glucose infusion during euglycemic clamp was lower (P < 0.05) at the end of the fattening period (7.39 mg x [kg.sup.-1] x [min.sup.-1]) than at baseline (21.21 mg x [kg.sup.-1] x [min.sup.-1]), in stable obese dogs, scFOS increased (P < 0.05) the rate of glucose infusion compared with control (7.77 vs. 4.72 mg x [kg.sup.-1] x [min.sup.-1]). Plasma insulin and triglyceride concentrations were greater in obese than in lean dogs but were not altered by scFOS. Whereas mRNA was not affected in food-deprived dogs, scFOS increased uncoupling protein 2 (P = 0.05) and tended to increase carnitine palmitoyl transferase 1 adipose mRNA levels during the postprandial period (P = 0.09). Adding 1% scFOS to the diet of obese dogs decreases insulin resistance and appears to modulate the transcription of genes involved in fatty acid or glucose metabolism.

Storage of energy as triglyceride in large adipose-specific lipid droplets is a fundamental need in all mammals. Efficient sequestration of fat in adipocytes also prevents fatty acid overload in skeletal muscle and liver, which can impair insulin signaling. Here we report that the Cide domain-containing protein Cidea, previously thought to be a mitochondrial protein, colocalizes around lipid droplets with perilipin, a regulator of lipolysis. Cidea-GFP greatly enhances lipid droplet size when ectopically expressed in preadipocytes or COS cells. These results explain previous findings showing that depletion of Cidea with RNAi markedly elevates lipolysis in human adipocytes. Like perilipin, Cidea and the related lipid droplet protein Cidec/FSP27 are controlled by peroxisome proliferator-activated receptor [gamma] (PPAR[gamma]). Treatment of lean or obese mice with the PPAR[gamma] agonist rosiglitazone markedly up-regulates Cidea expression in white adipose tissue (WAT), increasing lipid deposition. Strikingly, in both omental and s.c. WAT from BMI-matched obese humans, expression of Cidea, Cidec/FSP27, and perilipin correlates positively with insulin sensitivity (HOMA-IR index). Thus, Cidea and other lipid droplet proteins define a novel, highly regulated pathway of triglyceride deposition in human WAT. The data support a model whereby failure of this pathway results in ectopic lipid accumulation, insulin resistance, and its associated comorbidities in humans. adipocyte | Cide | diabetes | fat droplet | fat metabolism

To determine whether long-term melanocortinergic activation can attenuate the metabolic effects of a high fat diet, mice overexpressing an NH2-terminal POMC transgene that includes [alpha]- and [[gamma].sub.3]-MSH were studied on either a 10% low-fat diet (LFD) or 45% high-fat diet (HFD). Weight gain was modestly reduced in transgenic (Tg-MSH) male and female mice vs. wild type (WT) on HFD (P < 0.05) but not LFD. Substantial reductions in body fat percentage were found in both male and female Tg-MSH mice on LFD (P < 0.05) and were more pronounced on HFD (P < 0.001). These changes occurred in the absence of significant feeding differences in most groups, consistent with effects of Tg-MSH on energy expenditure and partitioning. This is supported by indirect calorimetry studies demonstrating higher resting oxygen consumption and lower RQ in Tg-MSH mice on the HFD. Tg-MSH mice had lower fasting insulin levels and improved glucose tolerance on both diets. Histological and biochemical analyses revealed that hepatic fat accumulation was markedly reduced in Tg-MSH mice on the HFD. Tg-MSH also attenuated the increase in corticosterone induced by the HFD. Higher levels of Agrp mRNA, which might counteract effects of the transgene, were measured in Tg-MSH mice on LFD (P = 0.02) but not HFD. These data show that long-term melanocortin activation reduces body weight, adiposity, and hepatic fat accumulation and improves glucose metabolism, particularly in the setting of diet-induced obesity. Our results suggest that long-term melanocortinergic activation could serve as a potential strategy for the treatment of obesity and its deleterious metabolic consequences. melanocyte-stimulating hormone; melanocortins; proopiomelanocortin; obesity; hepatic steatosis; diabetes doi:10.1152/ajpendo.00555.2006.

Adipose tissue inflammation has recently been linked to the pathogenesis of obesity and insulin resistance. C1 complex comprising three distinct proteins, C1q, C1r, and C1s, involves the key initial activation of the classic pathway of complement and plays an important role in the initiation of inflammatory process. In this study, we investigated adipose expression and regulation of C1 complement subcomponents and C1 activation regulator decorin in obesity and insulin resistance. Expression of C1q in epididymal adipose tissue was increased consistently in ob/ob mice, Zucker obese rats, and high fat-diet-induced obese (HF-DIO) mice. Decorin was found to increase in expression in Zucker obese rats and HF-DIO mice but decrease in ob/ob mice. After TZD administration, C1q and decorin expression was reversed in Zucker obese rats and HF-DIO mice. Increased expression of C1 complement and decorin was observed in both primary adipose and stromal vascular cells isolated from Zucker obese rats. Upregulation of C1r and C1s expression was also perceived in adipose cells from insulin-resistant humans. Furthermore, expression of C1 complement and decorin is dysregulated in TNF-[alpha]-induced insulin resistance in 3T3-L1 adipocytes and cultured rat adipose cells as they become insulin resistant after 24-h culture. These data suggests that both adipose and immune cells are the sources for abnormal adipose tissue production of C1 complement and decorin in obesity. Our findings also demonstrate that excessive activation of the classic pathway of complement commonly occurs in obesity, suggesting its possible role in adipose tissue inflammation and insulin resistance. C1 complement; gene expression doi:10.1152/ajpendo.00664.2006

Activin and myostatin are related members of the TGF-[beta] growth factor superfamily. FSTL3 (Follistatin-like 3) is an activin and myostatin antagonist whose physiological role in adults remains to be determined. We found that homozygous FSTL3 knockout adults developed a distinct group of metabolic phenotypes, including increased pancreatic islet number and size, [beta] cell hyperplasia, decreased visceral fat mass, improved glucose tolerance, and enhanced insulin sensitivity, changes that might benefit obese, insulin-resistant patients. The mice also developed hepatic steatosis and mild hypertension but exhibited no alteration of muscle or body weight. This combination of phenotypes appears to arise from increased activin and myostatin bioactivity in specific tissues resulting from the absence of the FSTL3 antagonist. Thus, the enlarged islets and [beta] cell number likely result from increased activin action. Reduced visceral fat is consistent with a role for increased myostatin action in regulating fat deposition, which, in turn, may be partly responsible for the enhanced glucose tolerance and insulin sensitivity. Our results demonstrate that FSTL3 regulation of activin and myostatin is critical for normal adult metabolic homeostasis, suggesting that pharmacological manipulation of FSTL3 activity might simultaneously reduce visceral adiposity, increase [beta] cell mass, and improve insulin sensitivity. activin | diabetes | metabolism | myostatin | [beta] cell

The present study included 3,358 observations of 675 bulls and heifers from the Iowa State University beef cattle breeding project. Data were collected over a 3-yr period between 1998 and 2000. Each year, cattle were scanned four to six times for ultrasound-predicted percentage of intramuscular fat (UPFAT) and other ultrasound traits, starting at a minimum age of 28 wk. The objective of the current study was to estimate variance components, heritability, and repeatability of UPFAT in young bulls and heifers. Data were subjected to random-regression animal models that included fixed effects of contemporary group, fixed Legendre polynomial of age at measurement, and random regression coefficients on Legendre polynomial of age at measurement for animals' direct genetic and direct permanent environmental effects. Phenotypic and genetic models involving different levels of polynomial fit for the animal component were considered. A model fitting a linear effect of Legendre polynomial of age at a measurement for animal direct genetic and direct permanent environmental effects and a homogeneous error variance described the present data adequately. Heritability of UPFAT ranged from 0.32 at 28 wk of age to a maximum of 0.53 at 63 wk. Repeatability of UPFAT increased from a minimum of 0.60 at ages of 28 to 39 wk to a maximum of 0.80 at ages 61 to 63 wk. Heritability and repeatability of yearling UPFAT were 0.50 and 0.71, respectively. With the exception of minor differences at earlier ages, fitting heterogeneous error variances did not have an effect on genetic parameter estimates for most ages of measurement. The present results showed an optimal heritability and repeatability of UPFAT measures around 52 wk and through at least 63 wk of age. This suggested that differences in UPFAT measures during this period also are good measures of differences in marbling genetic potential of Angus cattle. Key Words: Adipose Tissue, Beef Cattle, Composition, Heritability, Repeatability

Essential fatty acid (EFA) deficiency induces fat malabsorption, but the pathophysiological mechanism is unknown. Bile salts (BS) and EFA-rich biliary phospholipids affect dietary fat solubilization and chylomicron formation, respectively. We investigated whether altered biliary BS and/or phospholipid secretion mediate EFA deficiency-induced fat malabsorption in mice. Free virus breed (FVB) mice received EFA-containing ([EFA.sup.+]) or EFA-deficient ([EFA.sup.-]) chow for 8 wk. Subsequently, fat absorption, bile flow, and bile composition were determined. Identical dietary experiments were performed in multidrug resistance gene-2-deficient [[Mdr2.sup.(-/-)] mice, secreting phospholipid-free bile. After 8 wk, [EFA.sup.-]-fed wild-type [[Mdr2.sup.(+/+)]] and [Mdr2.sup.(-/-)]; mice were markedly EFA deficient [plasma triene (20:3n-9)-to-tetraene (20:4n-6) ratio >0.2]. Fat absorption decreased (70.1 [+ or -] 4.2 vs. 99.1 [+ or -] 0.3%, P < 0.001), but bile flow and biliary BS secretion increased in [EFA.sup.-] mice compared with [EFA.sup.+] controls (4.87 [+ or -] 0.36 vs. 2.87 [+ or -] 0.29 [micro]l*[min.sup.-1]*100 g body [wt.sup.-1], P < 0.001, and 252 [+ or -] 30 vs. 145 [+ or -] 20 nmol*[min.sup.-1]*100 g body [wt.sup.-1], P < 0.001, respectively). BS composition was similar in [EFA.sup.+]- and [EFA.sup.-]-fed mice. Similar to [EFA.sup.-] [Mdr2.sup.(+/+)] mice, [EFA.sup.-] [Mdr2.sup.(-/-)] mice developed fat malabsorption associated with twofold increase in bile flow and BS secretion. Fat malabsorption in [EFA.sup.-] mice is not due to impaired biliary BS or phospholipid secretion. We hypothesize that EFA deficiency affects intracellular processing of dietary fat by enterocytes. fat absorption; multidrug resistance gene-2; ATP-binding cassette; polyunsaturated fatty acids; phospholipid; bile salt

Results point out that the human winged helix/forkhead transcription factor gene FOXC2 regulates adipocyte metabolism, which lead to lean and insulin sensitive phenotype. Data indicate that high fat diet enhancement of FOXC2 levels counteract symptoms of obesity, hypertriglyceridemia, and insulin resistance.

In order to find genetic markers to improve the meat quality of pigs by breeding we studied the relationship between variation in the heart fatty acid-binding protein (H-FABP) gene (FABP3) and intramuscular fat (IMF) content. To estimate the effect of H-FABP, pigs from two Duroc populations were selectively mated in such a way that at least two genotypes were present in each litter. In total, data from 983 pigs and pedigree information from three preceding generations were analyzed. Offspring were tested for IMF content as well as backfat thickness (BFT), BW, and drip loss of the meat (DRIP). All pigs were assigned to H-FABP RFLP genotype classes either by the assessed genotype (75%) or based on a probability score determined according to genotypic information of their relatives (25%). Contrasts were detected between homozygous H-FABP RFLP genotype classes for IMF content (.4%, P < .05), BFT (.6 mm, P < .01), and BW (2.4 kg, P < 10). No significant contrasts were detected for DRIP. Results for IMF content, BFT, and BW were confirmed when only genotyped animals were analyzed. Variation in BFT partially explained the effect on IMF content. Although other closely linked genes on porcine chromosome 6 might be responsible for the observed effect, interference of the halothane gene was excluded because all parental animals were noncarriers. In conclusion, H-FABP RFLP can be used as markers to select for increased IMF content and growth in breeding programs. Key Words: Growth, Fat Metabolism, Genetic Markers, Meat Quality, Pigs

The body composition and core temperatures of heterozygous (+/fa) and fatty (fa/fa) Brown Norway hybrid pups were analyzed to determine the abnormal physiological traits of fa/fa compared to lean (+/+) littermates. The +/+ pups exhibited lesser body fat deposition compared to the +/fa pups. On the other hand, the fa/fa pups exhibited excessive fat deposition and decreased thermoregulatory thermogenesis during the first two weeks of postnatal development. However, fat deposition in +/fa was not similar to fat deposition in fa/fa pups.

Differences in fat deposition can be discernible in at an early age in rats homozygous for the obesity gene (Zucker rats) in comparison with hybrids of Zucker and Brown Norway rats. The plasma insulin concentration, hepatic glycogen and tissue triglycerides were not significantly different in these two groups when measured immediately before and after birth. However, homozygous Zucker rats show a higher rate of fat deposition than hybrid rats by the time they reach 7 to 16 days of age.

A study of the cloning and sequencing of mouse obese (ob) gene and its human homologue showed that the ob gene has a significant role to play in regulating fat mass in the body. The ob gene expression regulates the size of the adipose depot and falls in line with the lipostatic theory that ob gene forms a part of the signalling pathway that regulates food intake and energy expenditure. Mapping and identification of the ob gene and the formation and conservation of the sequence are also described.

While research studies have established that genetics influences the development of obesity, it is not known how strong this influence is and how it compares with the effect of environment and the way the individual was raised. Body-mass index, a measure of weight divided by height, is considered an indicator of leanness or obesity. Body-mass index was found to be similar between adopted children and their biologic parents and siblings, but not between the children and their adoptive parents. A study of twins was conducted to quantify the relative influences of genetics and environment on body-mass index. The subjects were 93 pairs of identical twins that were reared apart, 154 pairs of identical twins raised together, 218 pairs of fraternal twins reared apart, and 208 pairs of fraternal twins raised together. Body-mass index was highly correlated within the twin pair for both identical twins reared apart and those raised together, and the similarity between twins raised separately was only slightly less than the similarity between twins reared in the same household. The results indicate that inheritance has a substantial impact on body-mass index, while the environment during childhood has minimal or no impact. These findings are in agreement with those from previous studies of twins and adopted children. (Consumer Summary produced by Reliance Medical Information, Inc.)

It is well known that individuals of the same age and sex vary greatly in both the amount of total body fat and its distribution on the body. One reason for this variation in the population may be genetics; inheritance almost certainly influences the development of obesity. Scientists study the effect of genetics on body fat by comparing close relatives, and perhaps the most valuable information can be gleaned from examining identical twins. In theory, the influence of genetics should be the same for twins, and any differences between them should be due to environmental factors. Twelve pairs of identical twins, who were all sedentary young men, were studied to measure their responses to prolonged overfeeding. Six days a week for 100 days, each subject consumed 1,000 extra calories per day over and above their usual caloric intake, which had been measured for two weeks before the overfeeding began. Weight gain and the distribution of body fat were studied at the end of the overfeeding period; within the group as a whole, these results varied greatly. While the average weight gain was 18 pounds, the range was from 9 to 29 pounds. The results of overfeeding were significantly similar within the twin pairs, in terms of weight, percent body fat, fat mass, and subcutaneous (under the skin) fat. For these measures there was approximately three times as much variance among pairs in the group as there was within the twin pairs. The similarity within pairs was especially clear for abdominal fat and fat distribution. The authors conclude that the most probable reason for the similarities within twin pairs was the influence of genetics. Specifically, the tendency to store excess calories as either fat or muscle tissue may be inherited, as may be the metabolic rate while the body is at rest. (Consumer Summary produced by Reliance Medical Information, Inc.)

A question that has long concerned scientists and lay persons alike is whether obesity is inherited or caused by eating habits learned in childhood. The clearest answer to date is revealed in an article by Stunkard et al. which appears in the May 24, 1990 New England Journal of Medicine. Twins who had been reared either together or apart were evaluated for body-mass index, a measure of obesity. While both identical and fraternal twins were studied, the group that provided the most direct information about the inheritance of obesity was the identical twins reared apart. The similarity between two twins with identical genetic makeup who were raised in separate households gives an indication of the strength of genetic influences. These twins were very similar in body-mass index; it was found that genetics explained 70 percent of the differences in body-mass index and that childhood environment had either minimal influence or no impact at all. Other previous studies had also found that inheritance was very powerful in programming for obesity. But it would be unfortunate if these findings were interpreted as meaning that food habits in the home are unimportant. On the contrary, there is much evidence that childhood eating behavior influences whether the inherited tendency towards obesity is realized. Another study in the same issue of the New England Journal of Medicine, by Bouchard et al., involved intentional overfeeding of 12 pairs of identical twins to see if pairs of twins would gain the same amount of weight distributed in the same places on the body. There was much more variability in response to overfeeding between twin pairs than within pairs in this carefully controlled study. Again the strong influence of genetics was demonstrated, particularly in the accumulation of abdominal fat. This distribution of fat stores has been linked to risk of diabetes, high blood pressure and elevated blood cholesterol. (Consumer Summary produced by Reliance Medical Information, Inc.)

A research study found a genetically-transmitted metabolic defect that causes decreased production of fat-burning liver enzymes, linking this defect to obesity. This defect causes impairment of fat oxidation that leads to greater amount of calories unused for energy, which in turn leads to higher food intake. Other results of the research at Monel Chemical Senses Centerin Pennsylvania are discussed.

Research demonstrates a large cluster of genes associated with the metabolism of storage lipids. These genes are expressed by adipocytes and mutation in some of these genes lead to peripheral neuropathy.

Research has been conducted on peroxisome-proliferator-activated receptor delta. The authors demonstrate that targeted activation of this receptor in adipose tissue induces gene expressions which are important for fatty acid oxidation and energy dissipation.

Crossbred steers (n = 136) were used to assess breed differences in growth performance, carcass characteristics, fatty acid composition (total lipids and phospholipids), and palatability attributes of longissimus muscle. A multiple regression model was applied to crossbreeding data to estimate genetic differences between Simmental and Red Angus at the same level of backfat finish (10 mm). Simmental spent 71 more (P [is less than] 0.001) days on feed to acquire the same degree of backfat thickness as Red Angus, had heavier (P [is less than] 0.001) slaughter weights, larger (P = 0.002) longissimus muscle area, and increased (P = 0.023) lean yield. Average daily gain did not differ (P = 0.297) between breeds. Simmental were less (P = 0.012) efficient in converting feed to gain than Red Angus. Generally, there were few breed differences in palatability attributes for longissimus and semitendinosus muscles, with the exception of increased (P [is less than] 0.05) beef flavor scores for Simmental beef vs Red Angus beef across both muscles. For total lipids, concentrations of myristoleic acid (14:1), palmitoleic acid (16:1), and vaccenic acid (18:1n-7), along with n-6 to n-3 fatty acid (n-6:n-3) ratio, were greater (P [is less than] 0.05) in Simmental than Red Angus. In contrast, concentrations of margaric acid (17:0), eicosapentaenoic acid (20:5n-3), and total n-3 polyunsaturated fatty acids (n-3 PUFA) were greater (P [is less than] 0.05) in Red Angus than Simmental. For phospholipids, Simmental had lower (P [is less than] 0.05) amounts of 20:5n-3, docosahexaenoic acid (22:6n-3), and n-3 PUFA, with a greater (P = 0.017) n-6:n-3 ratio. Activity of [[Delta].sup.9]-desaturase enzyme in the conversion of palmitic acid (16:0) to 16:1 was greater (P = 0.001) in total lipids from Simmental as compared with Red Angus. A genetic basis for fatty acid differences is suggested, although the biological and practical significance needs to be demonstrated. Key Words: Beef Cattle, Breeds, Carcass Composition, Fatty Acids, Longissimus Dorsi, Palatability

Intramuscular fat content is a major determinant of meat quality in pigs. Previously, polymorphisms in the adipocyte and heart fatty acid-binding protein genes, A-FABP and H. FABP, have been significantly associated with genetic variation of intramuscular fat content in a Duroc pig population. Further support for the role of H-FABP but not for A-FABP was found in a Meishan crossbred population. However, the effect of closely linked genes could not be excluded in these analyses. To validate the role of A-FABP and H-FABP in intramuscular fat accretion, 153 pigs of a crossbred genotype were evaluated for the A-FABP and H-FABP polymorphisms, mRNA, and protein expression levels of both FABP genes and intramuscular fat content in the longissimus lumborum muscle. For H-FABP, statistical analyses showed significant differences in mRNA but not protein expression levels between H-FABP HaeIII PCR-RFLP genotype classes. Between these genotype classes, significant differences in intramuscular fat content were found within barrows but not in gilts. Moreover, H-FABP mRNA but not protein expression levels were significantly related to intramuscular fat content. For A-FABP genotype classes, no significant differences in mRNA and protein expression levels were found. However, a significant difference in intramuscular fat content was found within barrows but not in gilts. In addition, a significant relationship between A-FABP mRNA but not protein expression levels and intramuscular fat content was found. In conclusion, variation of intramuscular fat content could not be explained by differences in A-FABP and H-FABP mRNA and protein expression levels. However, this may be due to limitations of the assays used and(or) the inappropriateness of the time of sampling. Finally, results suggest that A-FABP and H-FABP expression are translationally rather than transcriptionally regulated. Key Words: Fat Metabolism, Genetic Markers, Loci, Meat Quality, Pigs

Green sunfish (Lepomis cyanellus) were injected (i.p.) with murine leptin over the course of two weeks to test the hypothesis that fish respond to leptin in a manner similar to mammals. Leptin is a 16 kDa protein hormone that controls metabolic rate and storage of body fat in mammals; we recently demonstrated the presence of leptin in fishes. If leptin signaling in fishes is similar to that in mammals, then administering leptin should lead to loss of body weight, decrease of appetite, and increase in fatty acid metabolism. Fish were divided into three groups of 10 each; the first group received 10 [micro]g leptin per day for 9 days and 20 [micro]g for 5 days (IP injection); the second group received an equal volume of phosphate-buffered saline, and the third group was simply handled. All groups lost weight, but total weight, % dry weight, % body fat, cardiosomatic index and hepatosomatic index were not different among groups. However, two indicators of fatty acid metabolism approximately doubled in the leptin treated group: CPT in liver(carnitine palmitoyl transferase; 0.57 [+ or -] 0.10; 0.28 [+ or -] 0.10; 0.25 [+ or -] 0.08 U/gm wet weight; LEPTIN, PBS, HANDLED, respectively; p [is less than] 0.05) and FABP in heart (fatty acid-binding protein; 85.6 [+ or -] 6.1; 53.2 [+ or -] 10.1; 32.6 [+ or -] 4.1% relative signal strength; LEPTIN, PBS, HANDLED, respectively; p [is less than] 0.05). These data indicate that the leptin signaling pathway is present in fish, and that it triggers an increase in fatty acid oxidation. Sponsored by OhioSeaGrant #735489 and NIH #1R15DK5811301 grants to RLL.

Research on the set point theory of body fat maintenance may debunk the theory that people become fat because they eat too much. A 1995 report in the New England Journal of Medicine supports the idea that people who gain or lose weight experience metabolic changes that bring the body back to its baseline weight. The set point mechanism is located in the brain, and animal studies have revealed the existence of a protein that circulates in the blood and somehow signals how much fat is present in the body. The brain knows how much fat the body should have, and institutes compensatory metabolic changes. The protein is produced by a gene called the obesity gene. Defects in the gene could produce defective protein, which might cause obesity. Changes in diet or exercise could also alter the set point.

Cloning of murine 'obese' (ob) gene producing a hormone secreted by fat cells may play an important role in regulating total fat mass through the formation of a signalling pathway. It is also possible that there exists a fat-derived satiety factor produced from adipose tissue, inhibiting food intake, thus controlling body weight. However, the origin of ob protein has not yet been traced to the adipose tissue, and so conclusions should not be drawn on the function of ob gene as the satiety factor.